Engineering protein nanocages for targeting melanocytes in skin for managing hyperpigmentation

What is it about?

Hyperpigmentation of the skin is caused by the upregulated production of melanin by the melanocyte cells, due to the effects of UV rays from the sun, environmental pollutants and hormonal imbalances. It is a major cosmetic concern that causes psychological distress requiring expensive treatments to manage the condition. Current formulations of therapeutic drugs and active molecules that are intended to be delivered to the melanocytes are not targeted, leading to inefficient delivery and undesirable side effects. There is a compelling need for delivery vehicles that target melanocytes to effectively regulate melanin production. Self-assembling protein nanocages (PNCs) are nature derived, versatile protein nanoparticle platforms that can offer safe and efficient delivery of active molecules. They can be engineered to display functional ligands to impart specific biological functions. In this work, E2 PNCs are engineered to display alpha-melanocyte-stimulating hormone (AlphaMSH) peptides as ligands for targeting and enhancing uptake by melanocytes. AlphaMSH-modified E2 at 500 picomolar concentration showed a 4-fold increase in melanocyte cell uptake compared to bare E2 PNCs in 2 hours. This increase was less pronounced in keratinocytes that constitutes over 95% of the skin. Competitive inhibition assay proves that the MC1R melanocyte cell surface receptor are involved in the uptake of E2 PNCs by mediating interaction with the displayed AlphaMSH peptides. PNCs can thus be used to deliver drugs and active molecules targeted to melanocytes for the management of hyperpigmentation.

Featured Image

Photo by Chermiti Mohamed on Unsplash

Photo by Chermiti Mohamed on Unsplash

Why is it important?

The current treatment modalities of hyperpigmentation are not effective due the lack of targeted delivery of drugs and active molecules. We have proposed a nature-derived delivery vehicle that is engineered to display ligands for targeting the melanocytes. These protein nanocages can reduce the required dose of therapeutics and the side effects on surrounding healthy cells. Protein nanocages can thus be used as carriers for drugs and active molecules leading to effective cosmetic formulations for managing skin conditions.

Perspectives